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Regeneration on a chip
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About two million deaths per year are caused by liver disease. The liver can regenerate when mature hepatocytes (the type of primary cell found in the liver) divide; however, although this process is well studied and characterized in rodents, it has not yet been explored in humans.
In a study recently published in the journal Proceedings of the National Academy of Sciences by a group of researchers led by Dr. Arnav Chhabra of the Massachusetts Institute of Technology, a three-dimensional (3D) “regeneration on a chip” model called structurally vascularized liver sets was presented to analyze regeneration (SHEAR), which is used to model multiple aspects of human liver regeneration.
SHEAR allows the control of hemodynamic alterations to mimic those that occur during injury and regeneration of the liver; supports the delivery of biochemical inputs, such as growth factors (cytokines) and paracrine interactions with endothelial cells between blood vessels and hepatic spheroids.
Figure: Model of molecular interactions in SHEAR. Courtesy: Chhabra, A. et al.
In their published results, the authors comment that stimulation with relevant cytokines amplified the secretory response and induced the entry into the cell cycle of primary human hepatocytes (PHH) integrated into the device. In addition, they identified endothelium-derived mediators that are sufficient to initiate PHH proliferation in this environment. Altogether, the data presented here underscore the importance of multicellular models that can recapitulate high-level tissue functions and demonstrate that the SHEAR device can be used to discover and validate conditions that promote human liver regeneration.
This device could be used in patients suffering from chronic diseases such as viral hepatitis, fatty liver, or cancer. It could even be used to stimulate the growth of a transplanted liver.
Writing by
Wendy López Romero, PhD
Research and Development Analyst at Drox Health Science. PhD in Medical and Pharmaceutical Biotechnology, Master in Molecular Biology. More than six years of experience in molecular biology, Immunology, Biochemistry and Proteomic, as well as in the development and validation of medical devices, with five publications in indexed journals.
Source:
Chhabra, A., Song, H. H. G., Grzelak, K. A., Polacheck, W. J., Fleming, H. E., Chen, C. S., & Bhatia, S. N. (2022). A vascularized model of the human liver mimics regenerative responses. Proceedings of the National Academy of Sciences, 119(28), e2115867119.
